生物昼夜节律的调控依赖于节律分子构成的转录-翻译反馈环路（TTLs），其中对节律分子PER3转录调控机制的研究并不是很透彻。我们前期实验发现，Maged1蛋白在不同时间点存在亚细胞分布动态变化，并与转录因子Neurod1相互作用。结合前人报道，Neurod1缺失小鼠的PER3转录水平下调，我们发现降低Maged1蛋白水平，PER3基因的转录水平也随之下降。因此在本项目中，我们拟通过干扰Maged1/Neurod1相互作用，结合CHIP、立体定位等生化相关分子技术和行为学检测，进一步解析两者相互作用对Neurod1核质穿梭的调节以及在细胞核中调控PER3基因转录的具体分子机制，该项目的研究有助于全面认识生物昼夜节律的调控机制，为治疗生物节律紊乱相关的睡眠疾病提供新的策略。

Circadian rhythm synchronizes the physiology and behavior of most animals to daily environmental oscillations, which is dependent on a negative transcriptional-translational feedback loop (TTLs). TTLs is composed of BMAL1, CLOCK, PER1/2/3 and CRY1/2, most of them has been studied out except PER3 gene in mammal. Here, we have revealed Maged1 shows dynamically subcellular localization at different time and the transcriptional activity of PER3 decreases with Maged1 knocking down. Moreover, Maged1 interacts with Neurod1. It has been reported that Neurod1 knock-out mice shows down-regulation of transcription level of PER3 gene. In this proposal, we will utilize a combination of approaches in cell biology, genetics, biochemistry, molecular biology and neurobiology, which to explore how subcellular localization of Neurod1 is affected by interacting with Maged1 and explain the mechanism of Maged1 regulating PER3 transcription in the nucleus. The potential results not only contribute to a deeper understanding of circadian rhythm, but also provide theoretical basis for the target site of drug design.